Priming system and method for dialysis systems

ABSTRACT

The application is directed to an extracorporeal blood processing system capable of using dialysate to prime the system. A plastic molded compact manifold supports molded blood and dialysate fluidic pathways along with relevant sensors, valves and pumps. The compact manifold is also disposable in one embodiment and can be detachably installed in the dialysis machine. A two-way valve in the manifold is used to direct the dialysate flow through the blood circuit to prime the circuit for use in treatment.

CROSS-REFERENCE TO RELATED APPLICATIONS

The present application is a continuation of U.S. patent applicationSer. No. 12/575,450, filed on Oct. 7, 2009, which is a continuation inpart of U.S. patent application Ser. No. 12/324,924, patented as U.S.Pat. No. 8,114,288, which relies on, for priority, U.S. ProvisionalPatent Application No. 60/990,959, entitled “System and Method ofChanging Fluidic Circuit Between Hemodialysis Protocol andHemofiltration Protocol”, filed on Nov. 29, 2007 and U.S. ProvisionalPatent Application No. 61/021,962, of the same title, filed on Jan. 18,2008. U.S. patent application Ser. No. 12/324,924, patented as U.S. Pat.No. 8,105,487 is incorporated herein by reference. Still further, thepresent invention incorporates by reference U.S. patent application Ser.No. 12/237,914, patented as U.S. Pat. No. 8,105,487 entitled “Manifoldsfor Use In Conducting Dialysis” and filed on Sep. 25, 2008 and U.S.patent application Ser. No. 12/245,397, published as U.S. PatentPublication No. 2009/0120864, entitled “Wearable Dialysis Systems andMethods”, filed on Oct. 3, 2008. Still further, the present applicationrelies on U.S. Provisional Application No. 61/103,274, filed on Oct. 7,2008, for priority and is herein incorporated by reference.

FIELD

The present specification is directed to systems and methods for priminga blood circuit with dialysate and, in particular, to a disposablemanifold that can be automatically switched between a priming mode ofoperation and a treatment mode of operation.

BACKGROUND

Hemodialysis is used for removing toxic wastes from the human body incases of renal failure. The patient's blood is temporarily broughtoutside of the body via tubes and passed through at least onesemi-permeable membrane, which may be a group of hollow fibers, in adialyzer. The semi-permeable membrane separates the blood from adialysate solution. Impurities from the blood pass through the membraneand into the dialysate solutions, primarily by osmotic pressure. Thecleansed blood is then returned to the body.

Standard dialysis treatment, using an installed apparatus in hospitals,comprises two phases, namely, (a) dialysis, in which toxic substancesand scoriae (normally small molecules) pass through the semi-permeablemembrane from the blood to the dialysis liquid, and (b) ultrafiltration,in which a pressure difference between the blood circuit and thedialysate circuit, more precisely a reduced pressure in the lattercircuit, causes the blood content of water to be reduced by apredetermined amount.

Dialysis procedures using standard equipment tend to be cumbersome aswell as costly, besides requiring the patient to be bound to a dialysiscenter for long durations. Conventional systems are also less reliablebecause of the necessity of using a myriad of tubes comprising the fluidcircuits of the purification systems, thus increasing the risks ofleakage and breakage. Accordingly there is need in the art for anextracorporeal blood processing system that can be operated inhemodialysis as well as hemofiltration modes, while at the same timeoffering reasonable portability to the patient. Such a portable dialysissystem should also be conducive to using disposable components. Further,there is also a need for novel manifolds for dialysis systems withintegrated blood purification system components, such as sensors, pumpsand disposables, as well as molded blood and dialysate flow paths toavoid a complicated mesh of tubing and to enhance the robustness of thesystem.

Conventional sorbent-based dialysis systems require the blood side ofthe disposable dialysis circuit to be primed with sterile saline beforeeach treatment prior to allowing the patient's blood to enter thecircuit. This is an important first step to purge the system of any air.In operation, the patient's blood enters tubing filled with the salinesolution and “chases” the saline solution to waste, after which dialysisbegins.

U.S. Pat. No. 4,661,246 describes a typical single access dialysisinstrument having a single catheter for receiving body liquids, adialyzer having a body liquid side with fluid inlet and fluid outletconnected to the catheter and further having a dialysate side with adialysate inlet and a dialysate outlet. The dialysis instrumentdescribed also includes storage means for holding a supply of liquid,including dialysate for use in the dialyzer.

US Patent application No. 20020017489 and U.S. Pat. No. 6,187,198describe systems and methods of priming a blood processing circuit inwhich both the retention of undesirable air bubbles and the risk ofcontamination is reduced.

US Patent application No. 20020017489 provides an arterial set and avenous set for blood flow between a blood processing unit and a patient.Each set has a main tube which carries a chamber in in-line flowrelationship, and a branch tube extending from the chamber to empty intoa drain receptacle. A portion of the branch tube extends through anupper wall of the chamber and projects for a distance into the chamberto spontaneously create an air bubble of desired operating volume abovea liquid level in the chamber. The patent application describes a methodof priming by passing a priming solution in a first direction of flowthrough at least one of the sets, to cause the priming solution to enteran in-line chamber carried by the one set in a flow direction that isretrograde to the normal direction of blood flow through the chamber.Next, the steps of removing air from the one set through a port andpassing the priming solution in a reverse direction of flow to the firstdirection are performed preferably simultaneously in order to completepriming of the blood processing unit.

US Patent Application 20070185430 provides a system and method forproducing purified replacement fluid in a unit used for renalreplacement therapy on a patient. The system can be used both to purifynon-purified fluid and to further purify sterile fluid contaminated(e.g., by touch contamination) during connection. The method employs theuse of a filter with a membrane, having a pore size smaller than thenon-purified and pyrogenic material to be filtered, separating a wasteside of the filter from a clean side, and a pump in fluid communicationwith a container of a replacement fluid in fluid communication with thewaste side of the filter, and a second container for holding purifiedreplacement fluid in fluid communication with the clean side of thefilter. The pump switches between a first direction that pumps fluid outof the first container and a second direction that removes waste fromblood.

All of the above mentioned patents and patent applications describevarious dialysis circuits and priming methods and are incorporatedherein by reference.

Conventionally, the priming procedure requires a minimum of a liter ofpriming fluid such as saline, a clamp, tubing, connectors and a polefrom which to hang the bag. A patient, or healthcare provider, mustconnect the line, open the clamp, close the clamp and dispose of thewaste. This is a problem because a) it requires a high skill level toset up and manage the priming procedure and b) it requires extramaterials. It would be preferred to use a more convenient priming fluidsource and to simplify the priming procedure such that trained healthcare professionals are not required to manage and/or handle the primingprocess.

SUMMARY OF THE INVENTION

The present specification discloses

The present specification further discloses a dialysis treatment systemcapable of operating in a priming mode and a treatment mode, comprisinga housing defining a cavity, which is capable of receiving a manifold.The manifold comprises a plastic substrate comprising a first layer anda second layer; a first flow path defined by a first surface of thefirst layer and a first surface of the second layer; a second flow pathdefined by a first surface of the first layer and a first surface of thesecond layer; a valve in fluid communication with both said first flowpath and said second flow path wherein said valve has first state and asecond state and wherein, when in said first state, the first flow pathand second flow path are in fluid isolation and when in said secondstate, the first flow path and second flow path are in fluidcommunication; and a valve interface physically attached to saidhousing, wherein said valve interface is configured to transmit a signalto said valve to cause said valve to switch between said first state andsaid second state.

Optionally, the manifold further comprises a first pump outlet, whereinsaid first pump outlet receives blood being pumped by a first pump, anda second pump outlet, wherein said second pump outlet receives dialysatebeing pumped by a second pump. Optionally, the valve is located adjacentsaid first pump outlet and said second pump outlet. Optionally, thevalve is in said first state, the first pump outlet and second pumpoutlet are in fluid isolation from each other. Optionally, when thevalve is in said second state, the first pump outlet and second pumpoutlet are in fluid communication with each other. Optionally, thedialysis treatment system further comprises a controller, wherein saidcontroller generates the signal to cause said valve to switch betweensaid first state and said second state. In one embodiment, thecontroller generates a signal to cause said valve to switch from saidfirst state to said second state in response to a command for thedialysis treatment system to operate in priming mode. In anotherembodiment, the controller generates a signal to cause said valve toswitch from said second state to said first state in response to acommand for the dialysis treatment system to operate in treatment mode.The dialysis treatment system further comprises a dialysate reservoirand the priming of said manifold is effectuated using dialysate fromsaid dialysate reservoir and not from a separate source of primingfluid.

In another embodiment, the present specification discloses a manifoldcapable of operating in a priming mode and a treatment mode, comprisinga plastic substrate comprising a first layer and a second layer; a firstflow circuit defined by a first surface of the first layer and a firstsurface of the second layer; a second flow circuit defined by a firstsurface of the first layer and a first surface of the second layer; avalve in fluid communication with both said first flow circuit and saidsecond flow circuit wherein said valve has first state and a secondstate and wherein, when in said first state, fluid from said first flowcircuit and cannot enter into said second flow circuit and when in saidsecond state, fluid from said first flow circuit can enter into saidsecond flow circuit; and an interface to receive a signal from a signalsource to cause said valve to switch between said first state and saidsecond state.

Optionally, the interface causes said valve to switch from said firststate to said second state in response to a signal to operate in primingmode. Optionally, the interface causes said valve to switch from saidfirst state to said second state in response to a signal to operate intreatment mode.

In another embodiment, the present specification discloses a primingprocess for priming a manifold within a dialysis machine for use in adialysis treatment, comprising the steps of: a) inserting said manifoldinto the dialysis machine, wherein said manifold comprises a bloodcircuit and a dialysate circuit, each defined by a substrate, and avalve in fluid communication with each of said blood circuit anddialysate circuit, wherein said valve has first state and a second stateand wherein, when in said first state, fluid from the dialysate circuitcannot enter into the blood circuit and when in said second state, fluidfrom the dialysate circuit can enter into the blood circuit; b) placingsaid valve in said second state; c) pumping dialysate through said bloodcircuit; d) placing said valve in said first state; and e) removingdialysate from said blood circuit.

Optionally, the dialysate is pumped from a dialysate reservoir and notfrom a separate source of priming fluid. Optionally, the valve is placedin said first state or second state by communicating a signal from acontroller located within the dialysis machine.

BRIEF DESCRIPTION OF THE DRAWINGS

These and other features and advantages of the present invention will beappreciated, as they become better understood by reference to thefollowing detailed description when considered in connection with theaccompanying drawings, wherein:

FIG. 1 shows an exemplary fluidic circuit for an extracorporeal bloodprocessing system;

FIG. 2 illustrates the structural elements of an exemplary compactmanifold, according to one embodiment of the present invention;

FIG. 3a provides a perspective view of the mid body component of thecompact manifold;

FIG. 3b provides a perspective view of the mid body component of thecompact manifold with exemplary dimensions;

FIG. 4 is a diagram detailing the fluidic circuit for the compactmanifold according to one embodiment of the present invention;

FIG. 5 illustrates an exemplary conductivity cell within the compactmanifold;

FIG. 6a shows an extracorporeal blood processing system according to oneembodiment of the present invention, with two two-way valves integratedinto the compact manifold that are used to determine the mode ofoperation of the system;

FIG. 6b illustrates in further detail, the circuit forhemodialysis/hemofiltration system according to one embodiment of thepresent invention;

FIG. 6c shows an exploded view of the extracorporeal blood processingsystem of the present invention, configured to operate in hemodialysismode;

FIG. 6d illustrates an embodiment where the extracorporeal bloodprocessing system of the present invention is configured to operate inhemofiltration protocol;

FIG. 6e shows another embodiment, where the compact manifold comprisesonly one two-way valve to determine the mode of operation of the system;

FIG. 7 illustrates an embodiment where the blood and dialysate circuitsare fully disposable, preassembled with the dialyzer, and areprepackaged in a kit together with the compact manifold;

FIG. 8 illustrates the installation of the compact manifold in aportable dialysis system;

FIG. 9 shows another view of a portable dialysis system, with themanifold successfully installed;

FIG. 10 is a schematic diagram showing one embodiment of the presentinvention in a dialysis mode; and

FIG. 11 is a schematic diagram showing one embodiment of the presentinvention in a dialysis priming mode.

DETAILED DESCRIPTION

While the present specification discloses embodiments in many differentforms, for the purpose of promoting an understanding of the principlesof the invention, reference will now be made to the embodimentsillustrated in the drawings and specific language will be used todescribe the same. It will nevertheless be understood that no limitationof the scope of the invention is thereby intended. Any alterations andfurther modifications in the described embodiments, and any furtherapplications of the principles of the invention as described herein arecontemplated as would normally occur to one skilled in the art to whichthe invention relates.

“Treat,” “treatment,” and variations thereof refer to any reduction inthe extent, frequency, or severity of one or more symptoms or signsassociated with a condition.

“Duration” and variations thereof refer to the time course of aprescribed treatment, from initiation to conclusion, whether thetreatment is concluded because the condition is resolved or thetreatment is suspended for any reason. Over the duration of treatment, aplurality of treatment periods may be prescribed during which one ormore prescribed stimuli are administered to the subject.

“Period” refers to the time over which a “dose” of stimulation isadministered to a subject as part of the prescribe treatment plan.

The term “and/or” means one or all of the listed elements or acombination of any two or more of the listed elements.

The terms “comprises” and variations thereof do not have a limitingmeaning where these terms appear in the description and claims.

Unless otherwise specified, “a,” “an,” “the,” “one or more,” and “atleast one” are used interchangeably and mean one or more than one.

For any method disclosed herein that includes discrete steps, the stepsmay be conducted in any feasible order. And, as appropriate, anycombination of two or more steps may be conducted simultaneously.

Also herein, the recitations of numerical ranges by endpoints includeall numbers subsumed within that range (e.g., 1 to 5 includes 1, 1.5, 2,2.75, 3, 3.80, 4, 5, etc.). Unless otherwise indicated, all numbersexpressing quantities of components, molecular weights, and so forthused in the specification and claims are to be understood as beingmodified in all instances by the term “about.” Accordingly, unlessotherwise indicated to the contrary, the numerical parameters set forthin the specification and claims are approximations that may varydepending upon the desired properties sought to be obtained by thepresent invention. At the very least, and not as an attempt to limit thedoctrine of equivalents to the scope of the claims, each numericalparameter should at least be construed in light of the number ofreported significant digits and by applying ordinary roundingtechniques.

Notwithstanding that the numerical ranges and parameters setting forththe broad scope of the invention are approximations, the numericalvalues set forth in the specific examples are reported as precisely aspossible. All numerical values, however, inherently contain a rangenecessarily resulting from the standard deviation found in theirrespective testing measurements.

The present invention eliminates the need to have a separate bag ofsterile saline and its associated hardware. In one embodiment, thepresent invention employs sorbent-generated dialysate, created when thedialysate side of the circuit is primed, as the priming fluid for theblood side. For purposes of explaining the invention, an exemplarymanifold in which the priming methods and systems of the presentinvention shall first be described.

FIG. 1 shows the fluidic circuit for an extracorporeal blood processingsystem 100, used for conducting hemodialysis and hemofiltration. In oneembodiment of the present invention, the system 100 is implemented as aportable artificial kidney (PAK), which may be used by a patient forconducting dialysis at home.

Referring to FIG. 1, the hemodialysis system comprises two circuits—aBlood Circuit 101 and a Dialysate Circuit 102. Blood treatment duringdialysis involves extracorporeal circulation through an exchanger havinga semi permeable membrane—the hemodialyser or dialyzer 103. Thepatient's blood is circulated in the blood circuit 101 on one side ofthe membrane (dialyzer) 103 and a dialysis liquid called the dialysate,comprising the main electrolytes of the blood in concentrationsprescribed by a physician, is circulated on the other side in thedialysate circuit 102. The circulation of dialysate fluid thus providesfor the regulation and adjustment of the electrolytic concentration inblood.

The line 104 from the patient which feeds impure blood to the dialyzer103 in the blood circuit 101 is provided with an occlusion detector 105which is generally linked to a visual or audible alarm (not shown) tosignal any obstruction to the blood flow. In order to preventcoagulation of blood, means 106, such as a pump, syringe, or any otherinjection device, for injecting an anticoagulant—such as heparin, intothe blood are also provided. A peristaltic pump 107 is also provided toensure flow of blood in the normal (desired) direction.

A pressure sensor 108 is provided at the inlet where impure blood entersthe dialyzer 103. Other pressure sensors 109, 110, 111 and 112 areprovided at various positions in the haemodialysis system that help keeptrack of and maintain fluid pressure at vantage points.

At the point where used dialysate fluid from the dialyzer 103 enters thedialysate circuit 102, a blood leak sensor 113 is provided to sense andwarn of any leakage of blood cells into the dialysate circuit. A pair ofbypass valves 114 is also provided at the beginning and end points ofthe dialysate circuit, so that under conditions of start up, or other asdeemed necessary by the operator, the dialyzer can be bypassed from thedialysate fluid flow but that flow maintained. Another valve 115 isprovided just before a priming/drain port 116. The port 116 is used forinitially filling the circuit with a dialysate solution, and to removeused dialysate fluid after and in some instances during dialysis. Duringdialysis, valve 115 may be used to replace portions of used dialysatewith high concentrations of for instance sodium with replenishment fluidof appropriate concentration so that overall component concentration ofthe dialysate is maintained at a desired level.

The dialysate circuit is provided with two peristaltic pumps 117 and118. Pump 117 is used for pumping dialysate fluid to the drain or wastecontainer, as well as for pumping regenerated dialysate into thedialyzer 103. Pump 118 is used for pumping out spent dialysate from thedialyzer 103, and pressuring it through the sorbent 119 and also forpumping in the dialysis fluid from port 116 for filling the system ormaintaining component concentration in the dialysate.

A sorbent type cartridge 119 is provided in the dialysate circuit, whichcontains several layers of materials, each having a specific role inremoving impurities such as urea and creatinine. The combination ofthese materials allows water suitable for drinking to be charged intothe system for use as dialysate fluid. It also allows closed loopdialysis. That is, the sorbent cartridge enables regeneration of freshdialysate from the spent dialysate coming from the dialyzer. For thefresh dialysate fluid, a lined container or reservoir 120 of a suitablecapacity such as 0.5, 1, 5, 8 or 10 liters is provided.

Depending upon patient requirement based on physician prescription,desired quantities of an infusate solution 121 can be added to thedialysis fluid. Infusate 121 is a solution containing minerals and/orglucose that help replenish minerals like potassium and calcium in thedialysate fluid at levels after undesired removal by the sorbent. Aperistaltic pump 122 is provided to pump the desired amount of infusatesolution to the container 120. A camera 123 may optionally be providedto monitor the changing liquid level of the infusate solution as asafety check warning of infusate flow failure.

A heater 124 is provided to maintain the temperature of dialysate fluidin the container 120 at the required level. The temperature of thedialysate fluid can be sensed by the temperature sensor 125 located justprior to the fluids entry in to the dialyzer. The container 120 is alsoequipped with a scale 126 for keeping track of the weight, and thereforevolume, of the fluid in the container, and a conductivity sensor 127,which displays the conductivity of the dialysate fluid. The conductivitysensor 127 provides an indication of the level of sodium in thedialysate.

A medical port 129 is provided before blood from the patient enters thesystem for dialysis. Another medical port 130 is provided before cleanblood from the dialyzer is returned to the patient. An air (or bubble)sensor 131 and a pinch clamp 132 are employed in the circuit to detectand prevent any air, gas or gas bubbles from being returned to thepatient.

Priming set(s) 133 is/are attached to the hemodialysis system that helpprepare the system by filling the blood circuit with sterile salinebefore it is used for dialysis. Priming set(s) may consist of shortsegments of tubing with IV bag spikes or IV needles or a combination ofboth pre-attached.

One of ordinary skill in the art would infer from the above discussionthat the fluidic circuit for a hemodialysis that a hemodialysis and/orhemofiltration system is a complex one and incorporates severalelements. If implemented in a conventional manner, the system wouldmanifest as a mesh of tubing and would be too complicated for a homedialysis user to configure and use.

Therefore, in order to make the system simple and easy to use at home bya patient, the present invention implements the system as a compactmanifold in which most components of the fluidic circuit shown in FIG. 1are integrated in a single piece of molded plastic or multiple pieces ofmolded plastic which are configured to connect together to form a singleoperative manifold structure.

FIG. 2 illustrates the structural elements of the compact manifold,according to one embodiment of the present invention. The disposablemanifold pumps and directs fluid flow while measuring pressure in keyareas. Those fluids include blood, dialysate, infusate andanticoagulant. In addition, the manifold provides features for detectingblood leakage from the dialyzer, detecting occlusion in the arterialline, and detecting air in venous line.

Referring to FIG. 2, in one embodiment, the compact manifold 200comprises a plurality of plastic layers with components fixedly attachedtherein. More specifically, the manifold 200 comprises the followingelements:

-   -   Back Cover 201    -   Pressure Transducer Membranes 202    -   Valve Membranes 203    -   Mid Body 204    -   Front Cover 205    -   Pump tube segments (not shown in FIG. 2)

The mid-body layer 204 contains molded in channels on one side. Thesechannels are completed by the front cover layer which is fixedlyattached to the mid-body by any number of methods, including ultrasonicwelding. This combined front cover-mid-body structure forms the majorpart of the fluid pathways within the manifold. On the opposite side ofthe mid-body 204 there are features that form surfaces for valving andpressure sensing, which communicate to the fluid pathways on the frontcover side of the manifold. The manifold includes elastomeric componentsfor valving and pressure sensing. These elastomeric components arecaptured between the back cover layer and mid-body layer through the useof ultrasonic welding and complete the fluid pathways throughout themanifold.

Referring to FIG. 2, in one embodiment, the manifold 200 comprises fivepressure transducer membranes 202 and three to four membranes 203 fortwo-way valves. In one embodiment, the two covers 201 and 205, and midbody 204 of the manifold 200 are molded of a polycarbonate material orABS (acrylonitrile butadiene styrene). The pressure transducer membranes202 and valve membranes 203 are molded of a common material, such asSantoprene, or more preferably Sarlink, which is a medical gradeelastomeric polymer. In one embodiment front and back covers 205 and 201may be molded of optically clear material, at least transparent tocertain preselected wavelengths of light, to allow for spectroscopicanalysis of the fluid(s) contained within.

Additionally, the manifold preferably includes four pumping components.These pumping components are segments of extruded PVC tubing formulatedand dimensioned to have properties optimized for pump use, particularlyroller pump use. This tubing is bonded to barbed fittings that areintegrally molded to the manifold mid-body. One of the four pumpingcomponents is for drawing blood from the patient's artery and pumping itthrough a dialyzer and back to the patient's vein. Two pumpingcomponents are for dialysate flow and one is for infusate delivery tothe dialysate fluid circuit. A separate syringe pump can be used forpumping anticoagulant into the arterial blood pathway, pre-dialyzer.

In one embodiment, the manifold further incorporates tubing ports,preferably in the range of 10-14 and more preferably 12 ports, forconnecting all the fluid pathways within the manifold to othercomponents in the disposable set including dialyzer, sorbent cartridge,bag reservoir, infusate container, patient blood lines, anticoagulant,sensors, priming line and drain, as further discussed below.

In one embodiment, the manifold is shaped like a capital “I”, with afirst segment and a second segment parallel to each other and aconnecting segment that a) is perpendicular to the first segment andsecond segment and b) serves to connect the first and second segments.In one embodiment, the connecting segment connects the middle of thefirst segment to the middle of the second segment, thereby making thedistance between the connecting segment and each end of the first andsecond segments equidistant. It should be appreciated that theconnecting segment can be placed at the ends of the first and secondsegment, thereby making a capital “C” or backwards “C”. The manifold canalso be rotated relative to the dialysis system and need not bepositioned as a capital “I”, e.g. it can be positioned on its side or atan angle. As shown in FIG. 3b , in an exemplary embodiment, the manifoldhas dimensions as follows: L1 and L2 are in the range of 4 to 7 inches,and preferably approximately 5.7 inches, L3 and L4 are in the range of0.5 to 1.5 inches, and preferably approximately 1 inch, L5 is in therange of 2.5 to 4.5 inches, and preferably approximately 3.5 inches, andL6 is in the range of 1 to 3 inches, and preferably approximately 1.8inches. While dimensions have been provided, it should be appreciatedthat the inventions disclosed herein are not limited to any specificdimension, or set of dimensions.

In one embodiment, the assembly process of the manifold 200 comprisesmating the back cover 201 to the mid body 204 while affixing themembranes 202 and 203 into place by having a first side of the membranesphysically attach or touch the mid body and having a second side of themembranes pass through holes, spaces, or voids 211 in the back cover201. Preferably, the second side of the membranes have a tieredstructure which permits a first tier to pass through the void 211 whilethe second tier remains between the back cover 201 and mid body 204.This affixes the membranes 202, 203 into the back cover 201.Furthermore, it is preferred for the mid body 204 to contain recessesinto which the first side of the membranes 202, 203 rest, therebyaffixing them to the mid body 204. In an alternate configuration, themembranes 202 and 203 may be co-molded to the back cover 201 in amulti-shot molding process.

One of ordinary skill in the art would appreciate that the variouscomponents of the manifold can be bound or affixed together using anysuitable means. In one embodiment, the seal between the midbody and backcover is achieved via ultrasonic welding or adhesive. Alternately laserwelding may be employed. The front cover is bonded to the other side ofthe mid body in a similar manner. Pump tubing segments are solventbonded into place in one embodiment, or in an alternate embodiment, thesegments may be laser welded using a laser absorbing additive in theplastic.

In one embodiment, the front cover is molded from BASF Terlux 2802HD,ABS, which is clear and will provide visibility to the fluid pathway.The clarity of the ABS will also provide a means for inspecting theintegrity of the ultrasonically welded surfaces. ABS is preferred forits biocompatibility as well as compatibility to ultrasonic welding.Additionally, the front cover can include a molded in textured surfaceto help facilitate a better bond between the front cover and themid-body. This textured surface is a chemical etching process that isknown to persons of ordinary skill in the art. One preferred texturedepth is 0.0045″. Other suitable textures can be laser etched as well.The surface to be welded on the front cover is designed with a 0.003″recess which translates to a 0.003″ raised surface on the mold. Thisprovides an accurate surface to receive the texturing. Once thetexturing takes place on the mold, the height of this 0.003″ surface islowered. Because of the peaks and valleys of the 0.0045″ texture depthit is assumed that the average would be half that amount or 0.00225″.The result would leave the mold in a steel safe condition of 0.00075″.

In one embodiment, the front cover provides blood flow directors in boththe arterial and venous pathways. These features are designed tominimize hemolysis. The blood flow directors provide for a consistentcross-sectional area throughout the pathway and minimize sharp edges towhich the blood would come in contact without their presence. The wallon the opposite side of the blood flow directors has been relieved toprovide a more consistent wall thickness in the molded plastic part.This will prevent sinks in this area, which could affect the surroundingwelded surfaces. In one embodiment, the front cover wall thickness is0.075″.

Optionally, the front cover has alignment holes are provided forassembly purposes to ensure that the front cover and mid-body areaccurately aligned during the ultrasonic welding process. The raisedbosses around the alignment holes help maximize contact with thealignment pins of the welding fixture so that the plastic does not meltas easily due to friction. These bosses do not touch and are not weldedto the mid-body to ensure that the hole is patent.

FIG. 3a provides a perspective view of the mid body component of thecompact manifold of the present invention. As is shown in FIG. 3, thecomplete blood and dialysate flow paths 301 of thehemodialysis/hemofiltration system are molded into the mid body.Accommodations for the various functional elements 302 of the bloodpurification system, such as pumps, valves and sensors are alsointegrated into the mid body section of the compact manifold.

The mid-body can be molded from BASF Terlux 2802HD, ABS. Anotheralternative ABS is Lustran 348, White. ABS was chosen for itsbiocompatibility as well as compatibility to ultrasonic welding. Themid-body along with the front cover provides the fluid path channels forthe manifold. The mid-body contains the energy directors for the buttjoint style ultrasonic welding. In one embodiment, the energy director'sdimensions are 0.019″ tall with a 0.024″ wide base. This results in across-sectional area of 0.00023 square inches. The width of the weldingsurface is 0.075″ resulting in a weld volume of about 0.003″×0.075″. Abutt joint style energy director is preferred over other styles, likeshear joints, tongue and groove, step joint, due to its simplicity andability to control the molded part geometry. Vents are provided in theweld geometry to prevent trapped gases from being forced through thewelds resulting in a poor weld that may leak.

The back cover side of the mid-body preferably provides a molded intextured surface to help facilitate a better bond between the back coverand the mid-body. This textured surface is a chemical etching processthat is known to persons of ordinary skill in the art. The preferredtexture depth is 0.0045″. Other suitable textures can be laser etched aswell. The surface to be welded on the mid-body is designed with a 0.003″recess which translates to a 0.003″ raised surface on the mold. Once thetexturing takes place on the mold, the height of this 0.003″ surface islowered. Because of the peaks and valleys of the 0.0045″ texture depthit is assumed that the average would be half that amount or 0.00225″.The result would leave the mold in a steel safe condition of 0.00075″.

The size of the components being welded can have a major impact on thesuccessfulness of the ultrasonic welding process. The larger the surfacearea, the more difficult the welding process. It is important that thewelding surfaces are accurately controlled. Consistent thickness in thefront and back covers is more important than flatness because a coverthat is off slightly on flatness will be pressed flat during the weldingprocess. Flatness on the mid-body is important due to the structuraldesign that would prevent it from being flattened during the weldingprocess. Due to these issues it is very important that the parts aredesigned correctly and not prone to anomalies like warpage, sinks,dimensional variations, etc. In addition, the mold construction andquality needs to match high standards that the parts will need to meet.It would follow that the molding process controls would require thehighest of standards as well.

The back cover can be molded from BASF Terlux 2802HD, ABS. The backcover contains the energy directors for the butt joint style ultrasonicwelding. The energy director's dimensions are 0.019″ tall with a 0.024″wide base. This results in a cross-sectional area of 0.00023 squareinches. The width of the welding surface is 0.075″ resulting in a weldvolume of about 0.003″×0.075″. This 0.003″ weld volume should beconsidered when determining the geometry of the assembled components.Vents are provided in the weld geometry to prevent trapped gases frombeing forced through the welds resulting in a poor weld that may leak.The alignment holes in the back cover are provided for assembly purposesto ensure that the back cover is accurately aligned to the mid-bodyduring the ultrasonic welding process. The alignment holes in the backcover also provide accurate alignment of the manifold and instrumentwhen properly loaded. The raised bosses around the alignment holes aredesigned to maximize contact with the alignment pins of the weldingfixture so that the plastic does not melt as easily due to friction.These bosses do not touch and are not welded to ensure that the hole ispatent.

Ultrasonic welding was chosen as the method for bonding the manifoldsthree major components because of the low cost of this manufacturingprocess. The relatively low equipment costs and cycle times to createthe weld attribute to this lower manufacturing cost. Once the parts areloaded into the fixture, the welding cycle with horn travel and removal,can be accomplished in seconds. The actual weld time is about onesecond. Other bonding methods include hot plate, laser, and UV adhesive.

Referring to FIG. 3a , in one embodiment, the mid body section 300 hasintegrated within it three 2-way valves 307, five pressure transducers306, an occlusion detector, an air bubble detector and a blood leakdetector. One of ordinary skill in the art would appreciate that thenumber and type of functional components that are integrated within themid body section 300 may be varied according to the requirement andapplication of the blood purification system and, therefore, can include1, 2, 3, 4, 6, 7, 8, 9, 10 or more pressure transducers, 1, 2, 4, 5, 6,or more 2-way valves, 0, 2, 3, 4, or more occlusion detectors, 0, 2, 3,4, or more air bubble detectors, 0, 2, 3, 4 or more blood leakdetectors. Additionally, the mid body section 300 comprises a pluralityof ports 303, 304.

The ports include internal ports 304 through which fluid flows via pumpsegments (not shown) from and between the first and second segments ofthe manifold 300. In one embodiment, the first segment has four internalports 304, two on each side of the point where the first segment andconnecting segment connect. It should be appreciated that the firstsegment can have 1, 2, 3, 5, 6, 7, or more internal ports. In oneembodiment, the second segment has four internal ports 304, two on eachside of the point where the first segment and connecting segmentconnect. It should be appreciated that the second segment can have 1, 2,3, 5, 6, 7, or more internal ports. Additionally, it is preferred thatthe position and location of the internal ports of the first segmentmirrors the position and location of the internal ports of the secondsegment. The ports also include external ports 303 to elements externalto the manifold 300. In one embodiment, the first segment has twoexternal ports 303. In one embodiment, the second segment has tenexternal ports 304. In one embodiment, the first segment has 1, 3, 4, 5,6, 7, 8, 9, 10, 11, 12, 13, 14, 15, or more external ports 303. In oneembodiment, the second segment has 1, 2, 3, 4, 5, 6, 7, 8, 9, 11, 12,13, 14, 15, or more external ports 304.

Incorporating fluid contacting elements into the manifold, as describedabove, enables the design of systems where reusable sensors are mountedin the dialysis machine to which the manifold is mated while necessarilydisposable fluid contacting elements are separated out and placed in themanifold, as described above. To ensure proper readings and measurementsare made, the fluid contacting elements and reusable sensors need to bealigned. Mating and alignment between the manifold and dialysis machineis critical with respect to positioning and pressure applied. Typicallysuch mating precision must provide for 0.001″ to 0.010″ tolerance in X,Y and Z directions and apply a mounting force in the range of 10-100 PSIto oppose fluid forces with the manifold. Such critical positioning isaccomplished by means of specially designed positioning surfaces on themanifold registering with complimentary positioning surfaces on thedialysis machine. Required forces are delivered by analysis and designof dialysis machine structure to allow for X and Y positions and Zdirection deflections of less than about 0.001″ to 0.010″ under allfluidic and mechanical pressures developed within the manifold duringoperation. Because the manifold contains many structures on onemonolithic substrate such critical alignment need only be done onceserving to position all features of the manifold with all matingfeatures of the dialysis machine.

Referring to FIG. 9, in one embodiment, the manifold 902 is mounted onthe vertical front panel 903 of the dialysis system 901. The manifold isaccurately located on this panel 903 by a plurality of alignmentmechanisms. The first alignment mechanism comprises a plurality ofalignment pins in the panel 903 that engage alignment holes in themanifold 902. The second alignment mechanism comprises at least onelatch that maintains the manifold 903 in a specific mounted positionuntil the door 906 is closed and the final accurate position isobtained. In one embodiment, the back cover of the manifold has twodesigned-in tabs at top and bottom. These tabs latch the manifold in afirst holding position prior to the door closure and subsequentplacement of the manifold's accurate position. The tabs enable alatching mechanism that can be manually released or by ball detents thatrequire forcibly removing the manifold by hand. In another embodiment,the latch mechanism comprises a spring loaded insertion and releasemechanism at the top of the back cover. This mechanism had a connectingrod between the top latch and a bottom latch. When the release mechanismat the top was activated the bottom latch released as well.

The third alignment mechanism comprises contoured guides 908 that directthe general position and configuration of the manifold 902. Thecontoured guides 908 are preferably shaped to mate with, match, orotherwise complement the physical structure of the manifold 902. In oneembodiment, the guides 908 are generally rectangular and configured tofit inside the space bounded by the sides of the first segment, secondsegment, and connecting segment. The fourth alignment mechanismcomprises a door 906 having at least one spring loaded pressure plate905 that captures the manifold 902 between the door 906 and front panel903, thereby applying adequate pressure for valving and pressuresensing. The door 906 also includes four pressure shoes that applyadequate pressure to the pumping components for rotary peristalticdelivery of fluids. It should be appreciated that one or more of thealignment mechanisms can be used, either alone or in combination, toachieve the requisite aligned and pressurized position for the manifold.It should further be appreciated that the alignment mechanisms areattached to the surface of a recessed region within the dialysis deviceenclosure. The recessed region comprises the front panel 903 that isrecessed relative to the dialysis device housing and is bounded by fourwalls (a first wall, a second wall, a third and a fourth wall) thatextends upward from the front panel 903 to meet and fixedly attach tothe dialysis device enclosure. The recess is sufficiently deep andconfigured to receive the door 906.

The mid-body channel size is nominally in the range of 0.190″ deep by0.190″ wide with 0.020″ radiuses at the bottom corners of the channel onthe mid-body side. The radius at the bottom corners of the channelshould be the maximum to prevent sinks from occurring under the channelwalls. These channel walls have valve and pressure diaphragm geometry onthe opposite side of the mid-body, which could be adversely affected bysink in these areas. In one embodiment, the fluid pathways are square.General design rule to prevent sink is that the wall thickness of a rib(channel wall in this case) should not be more than 50-60% of theadjacent wall, to which it is attached. The channel wall is 0.075″ andthe adjacent wall (main manifold structure) is 0.130″ resulting in 58%.The 0.190″×0.190″ dialysate channels transition to the 0.155″ tubingport through holes. This minimizes the accuracy required to align thefront cover to the mid-body and minimizes the potential for sinkscreated by the thicker walls which could affect sealing features on theopposite side of the mid-body. The same approach was taken foranticoagulant and infusate channels. Gentle curves are designed into thechannels to maximize laminar flow and minimize turbulent flow. In oneembodiment, the Anticoagulant and infusate channels, as discussed below,measure 0.190″ deep by 0.100″ wide.

In one embodiment, the mid-body has alignment holes for assemblypurposes to ensure that both the front cover and back cover areaccurately aligned to the mid-body during the ultrasonic weldingprocess. The raised bosses around the alignment holes maximize contactwith the alignment pins of the welding fixture so that the plastic doesnot melt as easily due to friction. These bosses do not touch and arenot welded to ensure that the hole is patent.

FIG. 4 is a diagram detailing the fluidic circuit for the compactmanifold according to one embodiment of the present invention. Thefluidic circuit comprises four peristaltic pumps P1 401, P2 402, P3 403and P4 404. It further comprises five pressure transducers S1 405, S2406, S3 407, S4 408 and S5 409, and a temperature sensor S6 410. In theembodiment illustrated in FIG. 4, three pairs of valves—V1A and V1B 411,V2A and V2B 412 and V3A and V3B 413 are integrated into the manifold.Grouped in this manner the pairs of six one way valves, 411 A,B, 412A,B, 413 A,B form three two way valve assemblies 411, 412, 413.

Pump tube segments 401, 402, 403, 404 are bonded into the compactmanifold. A number of ports are provided in the manifold, which connectwith tubes external to the manifold to allow the flow of various fluidsin and out of the manifold. These ports are connected to various tubesin the blood purification system for carrying fluids as follows:

-   -   Port A 415—blood to the dialyzer 430,    -   Port B 416—dialyzer output (used dialysate);    -   Port C 417—blood from the patient;    -   Port D 418—heparin for mixing in the blood;    -   Port E 419—reservoir output (fresh dialysate);    -   Port F 420—dialyzer input (fresh dialysate);    -   Port G 421—dialyzer output (blood);    -   Port H 422—patient return (clean blood);    -   Port J 423—connects to prime and drain line;    -   Port K 424—reservoir infusate input;    -   Port M 425—infusate in from infusate reservoir;    -   Port N 426—dialysate flow into sorbent.

In one embodiment, a tube segment, formed as a pathway molded into themanifold structure 400, connects the fluid flow of heparin, entering viaPort D 418, to the fluid flow of blood, entering via Port C 417. Thecombined heparin and blood flow through port 417 a, via pump 401, andinto port 417 b of the manifold 400. A pressure transducer is inphysical communication with a tube segment, formed as a pathway moldedinto the manifold structure 400, which, in turn, passes the blood andheparin fluid through Port A 415. Fluid flow out of the manifold 400 atPort A 415 passes through dialyzer 430, which is external to themanifold 400. The dialyzed blood passes back into the manifold 400through Port G 421 and into a tube segment, formed as a pathway moldedinto the manifold structure 400, that is in physical communication withpressure transducer 407. Fluid then passes from the tube segment throughPort H 422 and into a patient return line.

Separately, dialysis fluid enters the manifold 400 from a reservoir viaPort E 419. Fluid in the reservoir has infusate in it, which enters themanifold 400 via Port M 425, passes through a tube segment, formed as apathway molded into the manifold structure 400, through another port 425a, through a pump 402, and back into the manifold 400 via port 425 b.The infusate passes through a tube segment, formed as a pathway moldedinto the manifold structure 400, and out the manifold 400 at Port K 424,where it passes into the reservoir. The dialysis fluid which entered themanifold via Port E 419, passes through a tube segment, formed as apathway molded into the manifold structure 400, through another port 419a, through a pump 403, and back into the manifold 400 via port 419 b.

The dialysate fluid passes into a tube segment, formed as a pathwaymolded into the manifold structure 400, which is in physicalcommunication with a pair of valves 411. A tube segment, formed as apathway molded into the manifold structure 400, passes the dialysatefluid to another pair of valves 413. The tube segment is in physicalcommunication with pressure transducers 408 and optional temperaturesensor 410. The dialysate fluid passes out of the manifold 400 throughPort F 420, and into a line that passes into the dialyzer 430.

A line out of the dialyzer 430 passes fluid back into the manifold 400through Port B 416 and into a tube segment, formed as a pathway moldedinto the manifold structure 400, that is in physical communication witha first pair of valves 411, a second pair of valves 412, and a pressuretransducer 406. The used dialysate fluid passes out of the manifold 400through port 426 b, through pump 404, and back into the manifold viaport 426 a. A tube segment in fluid communication with port 426 a is inphysical communication with pressure transducer 409 and passes fluidthrough Port N 426 and to a sorbent regeneration system.

The tubing ports are designed for circuit tubing 0.268″×0.175″ tubing oranticoagulant and infusate tubing 0.161″×0.135″. Preferably, the tubingports are bonded with a suitable solvent.

In one embodiment, the 2-way valve operate by having valve actuators,which are mounted on the instrument, compress an elastomeric diaphragmover a volcano seal to prevent dialysate flow through its respectivepathway. The volcano seal opening is approximately 0.190″ diameter tomatch the channel geometry. The cross-sectional pathway through theinterior of the valve is at least equivalent to 0.190″ diameter whenvalves are open. When the valve is in the closed position the valveactuator and elastomeric diaphragm consume most of the fluid path spacearound the volcano seal minimizing the potential for air entrapment.There are raised plastic features on the mid-body that minimize deadspace within the fluid path as well as help prevent diaphragm fromcollapsing around the center fluid path under negative pressureconditions. The elastomeric diaphragm has an o-ring feature around itsperimeter that fits into a groove on the mid-body surface. The o-ring iscompressed between the mid-body and back cover to form a fluid tightseal. The design provides for approximately 30% compression on theo-ring. The 2-way valves control the direction of dialysate flow throughthe manifold.

The mid-body contains structures that allow for fluid pressuremonitoring across diaphragms through the use of sensors in theinstrument. Fluid is allowed to flow from channels on the front coverside of the mid-body through inlet and outlet holes underneath thediaphragm on the back cover side. The cross-sectional pathway throughthe interior of the pressure sensing structure is at least equivalent to0.190″. The interior pathway is designed to minimize air entrapmentwhile providing adequate fluid contact with the diaphragm. Theelastomeric diaphragm has an o-ring feature around its perimeter thatfits into a groove on the mid-body surface. The o-ring is compressedbetween the mid-body and back cover to form a fluid tight seal. Thedesign provides for a 30% compression on the o-ring.

The valves and diaphragms can be made from a variety of differentmaterials and by different processes. In one embodiment, the elastomericcomponents are made from silicone. In another embodiment, theelastomeric components are made from a variety of thermoplasticelastomers. Two shot molding may be used to attach the valves anddiaphragms to the back cover. Two shot molding of valves and diaphragmswould remove the need to individually assemble these parts into themanifold therefore reducing labor costs and improve quality of themanifold assembly.

Pumping components in the manifold design have been defined as PVCheader tubing. These headers combined with rotary peristaltic pumpingsystem of the instrument provide the flow of blood, dialysate, andinfusate. The circuit tubing material for dialysate, infusate, andanticoagulant is preferably kink resistant, such as the tubing referredto as Colorite, Unichem PTN 780, (80A durometer) extruded by Natvar, allTEKNIplex companies. The tubing dimensions for the dialysate linesranges from 0.268″×0.189″ to 0.268″×0.175″.

As mentioned above, the compact manifold for the dialysis system alsoincludes a temperature sensor (Ref. 410 of FIG. 4). In one embodiment ofthe PAK, the temperature sensor is located in the reservoir assembly.However, the temperature sensor may also be located outside thereservoir assembly, and in such embodiments, it can be integrated intothe manifold, as shown in FIG. 4.

There are three major approaches using which temperature sensing can beintegrated into the manifold. One of ordinary skill in the art wouldappreciate that variations are possible with each approach, withouteffecting any significant change in the overall design of the manifold.These approaches are discussed as follows:

High Conductivity Fluid Contact:

In high conductivity direct fluid contact approach, a metal disk isbuilt into the wall of the manifold with a thermistor or any othersuitable temperature sensor known in the art placed in contact with thedisk on the dialysis machine side, and with fluid on the patient side.Fluid temperature may thus be monitored through the metal disk.

Conventionally, the temperature is monitored by placing a thermistordirectly in the fluid stream. Use of metal disk for monitoringtemperature in the present invention provides an advantage thatcontamination, and hence the need for cleaning of the thermistor isavoided.

A person of ordinary skill in the art would appreciate that a metal diskof any suitable metal, such as type 316 Stainless Steel may be used forthe purpose. Further, a thermistor of any make appropriate for thecurrent application may be employed. An exemplary thermistor is partnumber 10K 3A1A manufactured by BetaTherm.

In one embodiment, the metal disk is for single patient use anddisposable, and the thermistor is part of the dialysis machine and isreused.

Medium Conductivity Fluid Contact:

The pressure transducer membranes (Ref. 202 of FIG. 2) of the compactmanifold are relatively thin and constructed of a medium thermalconductivity material. Thickness of typically 0.040″ are used and canvary from 0.005″ to 0.050″ The thinner the material and the higher thethermal conductivity, the more accurately the pressure transducermembranes will transmit temperature of the dialysis fluid to thepressure transducer mounted inside the dialysis machine. By design theyare in direct contact with the pressure transducer on the machine sideand the fluid on the patient side. Placing a suitable temperature sensorinside the pressure transducer allows monitoring the fluid temperature.Certain pressure transducers known in the art already include atemperature sensor for correction of the transducer due to temperaturedrift. Such pressure transducers with temperature sensing feature can beused for the purpose of present application. An exemplary combinationpressure—temperature sensor is model MPT40 manufactured by MicronInstruments. Employing such a combination of sensors avoids directcontact of the fluid measured and reduces the number of components inthe manifold. This provides an alternative to the metal disk, as used inthe previous approach.

Indirect Optical Temperature Measurement

If the plastic wall of the manifold fluid path is of limited thickness,such as approximately 0.020″, then the plastic wall will equilibrate intemperature to the fluid inside the manifold. Under such conditions anon contact optical temperature measurement can be made from outside ofthe thinned wall, and fluid temperature within can be determined. Anexemplary non contact optical temperature sensor is part number MLX90614manufactured by Melxis. The non contact approach provides the advantagethat it requires no additional parts in the manifold. The onlyrequirement is a thin section in the fluid path walls. This approachprovides low cost and still maintains single patient use safetyfeatures.

Apart from pressure transducers and temperature sensor, other sensorsmay also be included for integrating with the compact manifold. Theseother sensors include, but are not limited to, ammonia sensor, pH sensorand conductivity sensor. The ammonia and pH sensors may be integrated asindividual sensors into the manifold, or as a single ‘module’ thatcomprises both the sensors.

One possible implementation for an integral conductivity sensor in themanifold is as a conductivity cell with electrical pins contacting thedialysate fluid. The technical details of an exemplary conductivity cellare shown in FIG. 5. Referring to FIG. 5, the conductivity cell 500comprises bias pins 501 for applying a small, constant current to thefluid. Sensing pins 502 detect the voltage in the fluid, wherein themagnitude of the detected voltage is dependent on the conductivity andtemperature of the fluid. The temperature is measured using a thermistor503 placed next to the conductivity cell 500. Alternately thetemperature can be determined by one of the means disclosed above.Knowing the values of the measured temperature and voltage at thesensing pins 502, conductivity of the fluid can be determined.

The current applied through the bias pins 501 can be DC or an AC signaland is generally in the 50-100 kHz frequency range. In one embodiment,the magnitude of the applied current is of the order of 10 mA. Sensingpins 502 are generally depth positioned during manufacture of theconductivity cell, typically to a depth of +/−0.001 inch with calsolution in the cell. The thermistor 503 has a typical accuracy of 0.5Deg C.

The conductivity cell can be built into a dialysate fluid passage of thecompact manifold by driving or molding in place conductive pins (biaspins and sensing pins) into the manifold body such that they come incontact with the dialysate but do not allow dialysate to leak out of themanifold.

In one embodiment, sensing for blood leakage, air bubbles, and/orocclusion is achieved by including optical sensors in the dialysismachine which attach to, and around, pre-defined areas of the manifold.Referring back to FIG. 3a , the manifold 300 comprises a plurality oftubing support brackets 322 which facilitate accurately placing thecircuit tubing into optical sensors, such as Optek sensors, that areseparately mounted in the instrument when the manifold is installed andthe door is shut. The sensors provide means for detecting occlusion inthe arterial line, blood leak in the blood line downstream of thedialyzer and air detection in the venous blood line. The bracketsrestrain the tubing on one side of the sensor while the tubing port doesthe restraining on the other side of the sensor. These optical sensorsare U shaped devices into which the tubing is forced when the manifoldis installed. The tubing support brackets provide support for the tubingso that all three of these sensors are loaded with the same motion asloading the manifold, with no extra effort on the user's part.

As mentioned earlier, the extracorporeal blood processing system of thepresent invention is implemented as a portable artificial kidney (PAK)that is capable of operating in hemodialysis or hemofiltrationconfiguration as required. To allow the user to select the desired modeof operation (hemodialysis or hemofiltration), in one embodiment thesystem is provided with two-way valve(s). These valves can be actuatedby a user to direct dialysate flow either through the dialyzer in onemode of operation or to deliver infusate grade dialysate flow directlyto a patient, in a second mode of operation. These two-way valves canalso be integrated with the compact manifold of the dialysis circuit.This is illustrated in FIG. 6a . It should be noted that in FIGS. 6athrough 6e , for the purpose of clarity, corresponding elements have thesame numbers.

Referring to FIG. 6a , the extracorporeal blood processing system 600comprises a plastic molded compact manifold 610 that encapsulates aplurality of molded blood and dialysate fluidic paths as well as aplurality of sensors, valves and fluidic pumps. The dialyzer 605 whenconnected to the arterial blood tube 601 and venous blood tube 602 ofmanifold 610 completes the blood circuit of system 600. In oneembodiment, the dialyzer 605 is disposable. Two lines—603 and 604, areused for circulating spent and fresh dialysate respectively. Foroperating the system 600 in either of the two modes (hemodialysis andhemofiltration), a two-way valve 645, and a backup two-way valve 646 areprovided. Back up valve 646 is employed because the dialysate used inhemodialysis is not sterile and not infusion grade while the fluid usedin hemofiltration is. In the event of operation in hemodialysis mode anda leak or other failure of valve 645, valve 646 provides doubleprotection against that fluid being pumped into the patient bloodstream. Inclusion of backup valve 646 allows the use of one manifold forboth hemodialysis and hemofiltration safely. As noted above two wayvalves such as backup valve 646 are composed of two single valves. Inthis case both one way valves are in series and so by closing both portsof two way valve 646 double protection is afforded preventing dialysatefrom entering the blood stream. In an alternate embodiment a manifoldcan be made that is only intended for hemodialysis, having no connectionbetween dialysis fluid circuit and blood circuit and valve 646 be safelyeliminated.

FIG. 6b illustrates in further detail, the circuit forhemodialysis/hemofiltration system according to one embodiment of thepresent invention. Referring to FIG. 6b , the spent dialysate and freshdialysate tubes 603 and 604 respectively are connected to a dialysateregeneration system 606 thereby completing the dialysate circuit of thesystem 600. The dialysate regeneration system 606 further comprisesdisposable sorbent cartridges 615 and a reservoir 634 to hold dialysatecleansed by cartridges 615. Other components of the system shown in FIG.6b , and their functionality is explained with reference to FIG. 6c ,which shows an exploded view of the extracorporeal blood processingsystem 600 configured to operate in hemodialysis mode. Correspondingelements in FIGS. 6b and 6c have the same numbers.

Referring to FIGS. 6b and 6c , there are two fluid circuits—bloodcircuit 620 and dialysate circuit 625. Blood circuit 620 comprises aperistaltic blood pump 621 that draws a patient's arterial impure bloodalong the tube 601 and pumps the blood through dialyzer 605. A syringedevice 607 injects an anticoagulant, such as heparin, into the drawnimpure blood stream. Pressure sensor 608 is placed at the inlet of theblood pump 621 while pressure sensors 609 and 611 are placed upstreamand downstream of the dialyzer 605 to monitor pressure at these vantagepoints. As purified blood flows downstream from the dialyzer 605 andback to the patient, a blood temperature sensor 612 is provided in theline to keep track of temperature of the purified blood. An aireliminator 613 is also provided to remove accumulated gas bubbles in theclean blood from the dialyzer. A pair of air (bubble) sensors (oroptionally a single sensor) 614 and a pinch valve 616 are employed inthe circuit to prevent accumulated gas from being returned to thepatient.

The dialysate circuit 625 comprises two dual-channel dialysate pumps626, 627. Dialysate pumps 626, 627 draw spent dialysate solution fromthe dialyzer 605 and the regenerated dialysate solution from reservoir634 respectively. At the point where used dialysate fluid from thedialyzer 605 enters the dialysate circuit 602, a blood leak sensor 628is provided to sense and prevent any leakage of blood into the dialysatecircuit. Spent dialysate from the outlet of the dialyzer 605 then passesthrough the bypass valve 629 to reach two-way valve 630. A pressuresensor 631 is placed between the valves 629 and 630. An ultrafiltratepump 632 is provided in the dialysate circuit, which is operatedperiodically to draw ultrafiltrate waste from the spent dialysate andstore it in an ultrafiltrate bag 633, which is emptied periodically.

As mentioned previously, spent dialysate is regenerated using sorbentcartridges. The dialysate regenerated by means of sorbent cartridge 615is collected in a reservoir 634. The reservoir 634 includes conductivityand ammonia sensors 661 and 662 respectively. From the reservoir 634,regenerated dialysate passes through flow restrictor 635 and pressuresensor 636 to reach a two-way valve 637. Depending upon patientrequirement, desired quantities of infusate solution from the reservoir650 and/or concentrate solution from the reservoir 651 may be added tothe dialysis fluid. Infusate and concentrate are sterile solutionscontaining minerals and/or glucose that help maintain minerals likepotassium and calcium in the dialysate fluid at levels prescribed by thephysician. A bypass valve 641 and a peristaltic pump 642 are provided toselect the desired amount of infusate and/or concentrate solution and toensure proper flow of the solution into the cleansed dialysate emanatingfrom the reservoir 634.

The dialysate circuit comprises two two-way valves 630 and 637. Thevalve 630 directs one stream of spent dialysate to a first channel ofdialysate pump 626 and another stream of spent dialysate to a firstchannel of dialysate pump 627. Similarly, valve 637 directs one streamof regenerated dialysate to a second channel of dialysate pump 626 andanother stream of regenerated dialysate to a second channel of dialysatepump 627.

Streams of spent dialysate from pumps 626 and 627 are collected bytwo-way valve 638 while streams of regenerated dialysate from pumps 626and 627 are collected by two-way valve 639. The valve 638 combines thetwo streams of spent dialysate into a single stream that is pumped viapressure sensor 640 and through sorbent cartridges 615 where the spentdialysate is cleansed and filtered, collected in the reservoir 634. Thevalve 639 combines the two streams of regenerated dialysate into asingle stream, which flows to the two-way valve 645 through a bypassvalve 647. A pressure sensor 643 and a dialysate temperature sensor 644are provided on the dialysate flow stream to the two-way valve 645.

By reversing the state of two way valves 630, 637, 638 and 639 the twopumps 626 and 627 are reversed in their action of one withdrawingdialysis fluid from the dialyzer 605 and the other supplying dialysisfluid to the dialyzer 605. Such reversal, when done periodically overshort periods of time relative to the dialysis session, insures thatover the longer period of the entire dialysis session the dialysatefluid volume pumped into the dialyzer equals the amount of fluid pumpedout and the only total fluid volume lost by dialysis circuit 625 is thatremoved by ultrafiltrate pump 632.

In hemodialysis mode, depicted in FIG. 6c two-way valve 645 allows theregenerated dialysate to enter dialyzer 605 to enable normalhemodialysis of the patient's blood. One side of valve 645 is closedleading to the patient's blood return line. Another two-way valve 646acts as a backup, keeping dialysate form the patient's blood line withboth ports of valve 646 closed even if valve 645 leaks or fails.

In hemofiltration mode of operation, depicted in FIG. 6d the two-wayvalve 645 can be actuated to direct a stream of fresh ultrapuredialysate from reservoir 652 through valve 646, now with both ports opento directly enter the stream of purified blood emanating from thedialyzer and flowing back to patient.

It should be noted by persons of ordinary skill in the art that thebackup two-way valve 646 is a redundant safety valve to ensure that inhemodialysis mode failure of one valve 645 does not result in infusionof regenerated dialysate directly into the patient. That is, both thevalves 645 and 646 are capable of being actuated by the user to allowfluid to be directed to the patient's venous blood line as a safetyconsideration. In one embodiment the two-way back-up valve 646 is asingle valve to allow or stop fluid flow.

It should be further noted by persons of ordinary skill in the art thatvalves as described in the description above are termed as ‘bypass’ or‘two-way’ depending upon their use. Thus, valves are termed ‘bypassvalves’ when they bypass something like the dialyzer. Otherwise they aretermed ‘two-way valves’ and simply direct the flow in at least twodirections. However, the bypass and two-way valves are identical inconstruction.

In one embodiment, the two-way valves used in the present invention arefabricated as elastomeric membranes that are pressed against an orificeby a mechanism contained inside the dialysis machine to stop flow havingfluid contact with the rest of the fluidic circuit.

As mentioned, two-way valves 645 and 646 can be used for changing themode of operation for the blood processing system. FIG. 6d shows anembodiment, in which the system 600 is configured as operating inhemofiltration protocol. Referring to FIG. 6d , fluid flow in blood anddialysate circuits 620 and 625 is depicted. Since the system isoperating in hemofiltration mode, therefore the spent dialysate tube 603is connected to a drain while the fresh, dialysate tube 604 is connectedto fresh ultrapure and injectable grade dialysate reservoirs 652. Freshdialysate through a ball-valve drip chamber 653 passes through a heaterbag 654 to flow into the fresh dialysate tube 604. The rest of theelements and fluidic paths of the blood and dialysate circuits 620, 625are similar to those of FIG. 6c , except that in hemofiltration protocolfresh dialysate or replacement fluid is introduced into the dialysatecircuit 625 as the spent dialysate is drained and not reused. Alsodepicted by grey shading in FIG. 6d in hemofiltration mode the infusatesubsystem incorporating components 642, 650, 641 and 651 is unused.

Referring to FIG. 6d , the blood circuit 620 comprises a peristalticblood pump 621 that draws a patient's arterial impure blood along tube601 and pumps the blood through dialyzer 605. An optional pump 607injects an anticoagulant, such as heparin, into the drawn impure bloodstream. Pressure sensor 608 is placed at the inlet of the blood pump 621while pressure sensors 609 and 611 are placed upstream and downstream ofthe dialyzer 605. Purified blood from the dialyzer 605 is pumped throughtube 602 past a blood temperature sensor 612, air eliminator 613 and Air(bubble) sensors 614 and back to a vein of the patient. A pinch valve616 is also placed to completely stop blood flow if air is sensed by thebubble sensor 614 in the line upstream of the pinch valve 616 therebypreventing the air from reaching the patient.

The dialysate circuit 625 comprises two dual-channel dialysate pumps626, 627. Dialysate pumps 626, 627 draw spent dialysate solution fromthe dialyzer 605 and the fresh dialysate solution from reservoirs 652respectively. Spent dialysate from the outlet of the dialyzer 605 isdrawn through blood leak sensor 628 and bypass valve 629 to reachtwo-way valve 630. Pressure sensor 631 is placed between the valves 629and 630. An ultrafiltrate pump 632 is operated periodically to drawultrafiltrate waste from the spent dialysate and store in anultrafiltrate bag 633 (that is emptied periodically). Fresh dialysatefrom the reservoirs 652 passes through flow restrictor 635 and pressuresensor 636 to reach two-way valve 637. Persons of ordinary skill in theart would realize that in this protocol infusate and concentrate is notneeded and accordingly elements 641, 642, 650, 651 associated with thosefunctions are shown “grayed out”. In the fluidic diagram of FIG. 6e thetwo-way valve 641 as well as pump 642 are depicted in grey indicatingthat they are not in use, but are part of the common manifold 610 ofFIG. 6 a.

The heater bag 654 raises the temperature of the fresh dialysatesufficiently so that the temperature of the ultrafiltered blood goingback to the patient from the dialyzer 605 or the overall temperature ofthe mixture of ultrafiltered blood from dialyzer 605 and the freshdialysate infused directly into the purified blood by actuating thevalves 645, 646 is equivalent to the body temperature of the patientthereby preventing any thermal shock.

FIG. 6e shows an alternative embodiment of the fluidic set where thebackup two-way valve 646 of FIGS. 6a through 6c is not used. Referringnow to FIG. 6e , the blood circuit comprises peristaltic blood pump 621that draws a patient's arterial impure blood along tube 601 and pumpsthe blood through dialyzer 605. A pump 607 injects an anticoagulant,such as heparin, into the drawn impure blood stream. Pressure sensor 608is placed at the inlet of the blood pump while pressure sensors 609 and611 are placed upstream and downstream of the dialyzer 605. Purifiedblood from the dialyzer 605 is pumped through tube 602 past a bloodtemperature sensor 612, air eliminator 613 and Air (bubble) sensor 614and back to a vein of the patient. A pinch valve 616 is also placedbefore circuit connection of the patient to completely stop blood flowif air is sensed by the Air (bubble) sensor 614 in the line upstream ofthe pinch valve 616 thereby preventing the air from reaching thepatient.

The dialysate circuit comprises two dialysate pumps 626, 627. Dialysatepumps 626, 627 draw spent dialysate solution from the dialyzer 605 andthe regenerated dialysate solution from reservoir 634 respectively.Spent dialysate from the outlet of the dialyzer 605 is drawn throughblood leak sensor 628 to reach bypass valve 629. Flow sensor 630 is oneof two flow sensors (the other being flow sensor 646) which determinethe volume of dialysate flowing through the circuit. Valve 630′ issimilar in construction to a two-way valve and is used to bypassdialysate pump 626. Valve 630′ is normally closed in the direction ofthe bypass. In the event of stopping of the dialysate pump 626, valve630′ is opened to direct flow around pump 626. Pressure sensor 631 isplaced between the flow sensor 630 and the valve 630′. During normalflow, the spent dialysate is pumped via pressure sensor 640 and throughsorbent cartridges 615 where the spent dialysate is cleansed andfiltered. The cleansed/filtered dialysate then enters reservoir 634. Anultrafiltrate pump 632 is operated periodically to draw ultrafiltratewaste from the spent dialysate and store in an ultrafiltrate bag (notshown) that is emptied periodically.

Regenerated dialysate from the reservoir 634 passes through flowrestrictor 635, dialysate temperature sensor 644, flow sensor 646 andpressure sensor 636 to reach two-way valve 645 through bypass valve 641.When the respective flow paths of bypass valves 629 and 645 and 641 areactivated they direct regenerated dialysate to bypass the dialyzer 605.Infusate and concentrate streams from infusate and concentratereservoirs 650, 651 are directed by infusate and concentrate pumps 642,643 into the cleansed dialysate emanating from the reservoir 634 and thespent dialysate downstream of flow sensor 630, respectively.

The two-way valve 645 determines what mode the system 600 is operatingin. Thus, in one mode of operation the two-way valve 645 allows theregenerated dialysate to enter dialyzer to enable normal hemodialysis ofthe patient's blood. In another mode of operation, the two-way valve 645is actuated to direct fluid flow of ultra pure infusate grade dialysisfluid into the venous blood line and directly to patient. Accordingly,the versatile valves enable the mode of operation to switch betweenhemofiltration and hemodialysis. For example, in hemofiltration shown inFIG. 6d infusible grade fluid is routed through the three valvesdirectly into the blood stream where valve 646 connects to the postdialyzer. In this mode valve 645 prevents the dialysate fluid fromentering the lower port of the dialyzer. In hemodialysis, shown in FIG.6,c valve 646 is closed and valves 647 and 645 route dialysate fluid tothe dialyzer.

It should be noted that while the embodiments of FIGS. 6c and 6erepresent two different flow control concepts. While the embodiment ofFIG. 6c uses pump swapping and a plurality of valves to control fluidvolume, the embodiment of FIG. 6e uses flow sensors 630 and 646 tocontrol fluid volume.

The use of a manifold for fluidic circuit of a hemodialysis systemenables the dialysis unit (portable artificial kidney, or PAK) to bemodular and portable, with improved functionality. The manifold can bemanufactured as a separate unit that can be easily installed into thedialysis unit. FIG. 7 illustrates an embodiment where the blood anddialysate circuits are fully disposable, and are prepackaged in a kit700. The kit includes the dialyzer 701, manifold 702, tubing 703, valves704 (as part of the manifold), reservoir bag 705, and other disposablecomponents.

FIG. 8 illustrates the manifold as installed in the dialysis machine.Referring to FIG. 8, the dialysis machine 801 has a front door 803 whichcan be widely opened to install the disposable components. Forinstallation, the manifold 804 simply needs to be inserted in the spaceprovided for the purpose in the dialysis unit 801. Installing thedialyzer 802 also involves a simple insertion in a designated recess.The front door 803 is provided with pump shoes that makes loading ofdisposable components very easy, as no pump tubing needs to be threadbetween roller and shoes. Further, this arrangement allows installingthe dialyzer 802 and the manifold 804 in a manner that ensures properalignment against non-disposable components such as pressure readers,sensors, and other components. This packaged, simple approach enableseasy disposables loading and cleaning of the system. It also ensuresthat the flow circuitry is properly configured and ready for use.

The present invention can operate in at least two different modes: apriming mode and a treatment mode, which can comprise other modes ofoperation (such as hemodialysis, hemofiltration, or, simply, anon-priming mode). With respect to an exemplary treatment mode andreferring concurrently to FIG. 4 and FIG. 10, a dialysis system 1000operating in dialysis mode comprises a dialyzer 1002, 430, sorbentregeneration system (e.g. cartridge) 1012, manifold 1010, 400, infusateor dialysate source 1016 entering into the manifold 1010, 400 throughPort M 425, and reservoir 1015 from which fresh dialysate is input backinto the manifold 1010, 400 via Port E 419. In operation, blood entersthe blood line 1001, into the manifold 1010, 400 through Port C 417,through a two-way valve 1021 which is in a first position, and into thedialyzer 1002. The purified blood exits the dialyzer 1002, 430, througha two-way valve 1022 which is in a first position, and into the manifold1010, 400 through Port G 421. The blood passes through the manifold,passing through a plurality of valves, as described above in relation tomanifold 400, 1010, and out of Port H 422 and into a blood line 1023entering the patient.

Concurrently, infusate or dialysate passing from a source 1016 passesinto the manifold 1010, 400, through Port M 425, through the manifold,out through Port F 420, into dialysate in-line 1024 and into dialyzer1002, 430. After passing through the dialyzer 1002, the dialysate passesthrough an out-line 1025 and back into the manifold 1010, 400 throughPort B 416 where it is routed to the sorbent-based dialysateregeneration system 1012 via Port N 426. Regenerated dialysate passesback through the manifold 1010, 430 via Port E 419 and recirculatedthrough the dialyzer 1002, 430 with new dialysate, if and when required.To manage dialysate fluid flow, a reservoir 1015 is used to storeregenerated dialysate, if and when needed. In one embodiment, thereservoir holds 5 liters of dialysate and has the capacity to hold up to10 liters of dialysate and effluent from the patient.

With respect to an exemplary priming mode and referring concurrently toFIG. 4 and FIG. 11, a dialysis system 1100 operating in priming modecomprises a dialyzer 1102, 430, sorbent regeneration system (e.g.cartridge) 1112, manifold 1110, 400, infusate source 1116, and reservoir1115. In operation, the bloodline from the patient (e.g. 1001 in FIG.10) into the manifold 1110, 430 is not connected and therefore, no bloodis flowing, or capable of flowing, through Port C 417 into the manifold1110, 400. Rather, dialysate passing from a source 1116 passes into themanifold 1110, 430 through Port M 425, out through Port B 416 andthrough a dialysate in-line 1124, which is connected to the two-wayvalve port 1122.

In a preferred embodiment, a single two-way valve is incorporated intothe physical body of the manifold and manipulated to switch between atreatment mode of operation and a priming mode of operation. In thisembodiment, a manifold comprises a two-valve which, if activated orswitched from a first positioned (e.g. closed) to a second position(e.g. open), causes a change to the internal flowpath of liquid withinthe manifold. As a result of this flowpath change, the blood anddialysate circuits, which, when the valve is closed, are fluidicallyisolated from each other, are now placed in fluid communication witheach other. Preferably, no additional valves or switches need to bemanipulated in order to achieve this state change, namely, to causeseparate blood and dialysate circuits to become fluidly connected.

The valve switch may be effectuated by any means known in the art,including by physically manipulating a mechanical control on the surfaceof the manifold or electronically through the operation of a dialysismachine causing a change to the valve state through an interface betweenthe dialysis machine, which has a controller to control the state of thevalve in accordance with a user selected operational mode, and a valveinterface integrated into the surface of the manifold. In oneembodiment, the present invention deploys a bi-stable magnet-drivenvalve, as disclosed in U.S. patent application Ser. No. 12/351,969,filed on Jan. 12, 2009 and incorporated herein by reference.

In a preferred embodiment, the dialysis machine comprises an interface,in the form of a graphical user interface with touch screen buttons,physical keypad, or mouse, which can be manipulated to cause a dialysismachine, as shown in FIGS. 8 and 9, loaded with a manifold to startoperation in either a treatment mode or priming mode. When instructed tooperate in treatment mode, the controller generates a signal (inresponse to that treatment mode command) to cause the manifold valve toswitch from an open, priming state to a closed, treatment state. Wheninstructed to operate in priming mode, the controller generates a signal(in response to that priming mode command) to cause the manifold valveto switch from a closed, treatment state to an open, priming state. Oneof ordinary skill in the art would appreciate that all of theaforementioned control and user command functions are effectuated byincorporating one or more processors, executing programming embodyingthe aforementioned instructions, which are stored in local memory.

Referring to FIG. 4, in one embodiment, the two-way or two-state valveis preferably located at position “V” between the outlet of pump 403 andthe outlet of pump 401. In treatment mode, the valve, which is in aclosed position, permits dialysate fluid flowing out of pump 403 tocirculate through the manifold, pass through Port F, and enter into thedialyzer 430. This dialysate circuit path is fluidically isolated fromthe blood circuit in which blood flows through pump 401 to circulate outof the manifold, pass through Port A, and enter into the dialyzer 430.Accordingly, in treatment mode, the valve ensures that the blood anddialysate circuits remain fluidly isolated.

In priming mode, the valve would be opened, thereby causing dialysatefluid flowing through pump 403 to pass through the manifold at Port A,into the dialyzer 430, out of dialyzer 430, and back into the manifoldat Port G and out of manifold at Port H. Accordingly, in the primingmode, the valve ensures that the dialysate circulates through the bloodcircuit, thereby placing the blood and dialysate circuits in fluidcommunication. Functionally, the manifold is placed in priming mode, bymanipulating the state of the two-way valve, preferably located atposition “V” in the manifold.

After a specified volume of dialysate is pumped into and through theblood circuit, the two-way valve is closed. Pumping of dialysate may ormay not continue. If continued, the fresh dialysate circulates throughthe dialysate circuit only. In the blood circuit, residual dialysateremains. To purge the dialysate from the blood circuit, a patient isconnected to the “From Patient Line” 1001, shown in FIG. 10 andtypically referred to as the arterial access line. The “To Patient Line”1923, typically referred to as the venous return line is either heldover a waste container or connected to a patient.

Placing the system in treatment mode, blood from the patient is drawninto the blood circuit, passing into the manifold via Port C, throughpump 401, out of the manifold at Port A, through dialyzer 430, back tothe manifold at Port G, and back out of the manifold at Port H. Theblood thereby causes the residual priming fluid to be ‘chased’ throughthe blood circuit, removing any remaining air pockets in the process,and into either a waste container or the patient, depending on theconnected state of the venous return line. After blood has completelyfilled the blood circuit, the system stops the blood pump or the userstops the pump manually. If not already connected, the venous returnline is then connected to the patient and the treatment continues.

In another embodiment, a filter, such as a 0.22μ filter, can be used tohelp remove any remaining undesirable substances if the sorbent-canisteris inadequate to produce essentially sterile dialysate. In oneembodiment, the filter is positioned in-line with the reservoir inputline, proximate to Port E of the manifold, and is used both duringpriming and operation.

By using this priming system, one avoids having to use an additional andseparate set of disposables to just prime the blood side of the circuit.In particular, the present invention eliminates the need for a separatesaline source, in particular a 1 liter bag of saline, and, accordingly,also eliminates the need for connectors and tubing to the separatesaline source, including dual-lumen spikes or single lumen spikes usedto connect blood lines to the saline.

While there has been illustrated and described what is at presentconsidered to be a preferred embodiment of the present invention, itwill be understood by those skilled in the art that various changes andmodifications may be made, and equivalents may be substituted forelements thereof without departing from the true scope of the invention.In addition, many modifications may be made to adapt a particularsituation or material to the teachings of the invention withoutdeparting from the central scope thereof. Therefore, it is intended thatthis invention not be limited to the particular embodiment disclosed asthe best mode contemplated for carrying out the invention, but that theinvention will include all embodiments falling within the scope of theappended claims.

We claim:
 1. A priming process for priming a first circuit and a secondcircuit used in a dialysis machine, said first and second circuitshaving a manifold and a dialyzer external to said manifold, said primingprocess comprising: inserting said manifold into the dialysis machine,wherein said manifold comprises a plurality of molded components whichare configured to connect together to form a single operative structurecomprising a portion of the first circuit, a portion of the secondcircuit and a compressible valve structure in fluid communication witheach of said first and second circuits, wherein said valve structure isone of said plurality of molded components and has a first state and asecond state, wherein, when in said first state, fluid from the firstcircuit cannot enter into the second circuit within said manifold and isseparated from a second fluid within said second circuit by asemi-permeable membrane within said dialyzer and when in said secondstate, said first fluid from the first circuit can enter into the secondcircuit within said manifold and said dialyzer; placing said valve insaid second state by removing pressure from said compressible valvestructure; pumping said first fluid through said first and secondcircuits within said manifold and dialyzer; placing said valve in saidfirst state by applying pressure to said compressible valve structure;and removing said first fluid from said second circuit, wherein a venousline and an arterial line of the manifold are connected to a patientwhen said valve is in said first state and wherein said venous line isnot connected to said patient and said arterial line is connected tosaid patient when said valve is placed in said second state.
 2. Thepriming process of claim 1 wherein the first circuit is a dialysatecircuit and wherein the second circuit is a blood circuit.
 3. Thepriming process of claim 2 wherein the fluid is dialysate and wherein,in said second state, the dialysate flows through the dialysate circuitand into the blood circuit.
 4. The priming process of claim 3 whereinthe dialysate is removed from the blood circuit upon completion of thepriming process.
 5. The priming process of claim 3 wherein the dialysateis pumped from a dialysate reservoir and not from a separate source ofpriming fluid.
 6. The priming process of claim 1 wherein said valve isplaced in said first state or second state by a controller, locatedwithin the dialysis machine, actuating a valve interface physicallyattached to said dialysis machine.
 7. The priming process of claim 6wherein said valve interface is configured to apply pressure to, orremove pressure from, said compressible valve structure upon actuationby said controller.
 8. A priming process for priming a plurality ofcircuits in a dialysis machine, said dialysis machine having a manifoldand a dialyzer external to said manifold, the priming process comprisingthe steps of: receiving said manifold into a cavity located in saiddialysis machine, wherein said manifold comprises a plurality of moldedcomponents which are configured to connect together to form a singleoperative structure comprising a dialysate circuit, a blood circuit anda compressible valve structure in fluid communication with each of saiddialysate and blood circuits, wherein said valve structure is one ofsaid plurality of molded components and has a treatment state and apriming state, wherein, when in said treatment state, dialysate from thedialysate circuit cannot enter into the blood circuit within saidmanifold and is separate from blood within said dialysate circuit by asemi-permeable membrane within said dialyzer and, when in said primingstate, fluid from the dialysate circuit can enter into the blood circuitwithin said manifold and said dialyzer; having said valve in saidpriming state by not applying pressure to said compressible valvestructure; pumping dialysate through said dialysate and blood circuitswithin said manifold and said dialyzer; placing said valve in saidtreatment state by applying pressure to said compressible valvestructure; and removing dialysate from said blood circuit, wherein avenous line and an arterial line of the manifold are connected to apatient when said valve is in said treatment state and, when said valveis placed in the priming state, said venous line is in fluidcommunication with a waste container and the arterial line is notconnected to the patient.
 9. The priming process of claim 8 wherein thedialysate is pumped from a dialysate reservoir and not from a separatesource of priming fluid.
 10. The priming process of claim 8 wherein saidvalve is placed in said treatment or priming state by a controller,located within the dialysis machine, that is configured to actuate avalve interface within said dialysis machine.
 11. The priming process ofclaim 10 wherein said valve interface is configured to apply pressureto, or remove pressure from, said compressible valve structure uponactuation by said controller.
 12. A priming process for use in adialysis treatment system, wherein said dialysis treatment systemcomprises a housing defining a cavity, said cavity capable of receivinga manifold, wherein the manifold comprises a plurality of plastic moldedcomponents which are configured to connect together to form a singleoperative structure comprising a first layer and a second layer, a firstflow path defined by a first surface of the first layer and a firstsurface of the second layer, a second flow path defined by a firstsurface of the first layer and a first surface of the second layer, anda valve in fluid communication with both said first flow path and saidsecond flow path wherein said valve has a first state and a second stateand wherein, when in said first state, the first flow path and secondflow path are in fluid isolation and when in said second state, thefirst flow path and second flow path are in fluid communication, and acompressible valve structure in said manifold and positioned over saidvalve, said priming process comprising the steps of: receiving saidmanifold into the cavity; having said valve in said second state by notapplying pressure to said compressible valve structure; pumping fluidthrough said first and second flow paths; placing said valve in saidfirst state by applying pressure to said compressible valve structure;and removing fluid from said second flow path, wherein a venous line andan arterial line are in fluid communication with both the manifold andthe patient when said valve is in first state and wherein said venousline is in fluid communication with a waste container and said arterialline is not connected to said patient when said valve is placed in asecond state.
 13. The priming process of claim 12 wherein the first flowpath is a dialysate flow path and wherein the second flow path is ablood flow path.
 14. The priming process of claim 13 wherein the fluidis dialysate and wherein, in said second state, the dialysate flowsthrough the dialysate flow path and into the blood flow path.
 15. Thepriming process of claim 14 wherein the dialysate is removed from theblood flow path upon completion of the priming process.
 16. The primingprocess of claim 14 wherein the dialysate is pumped from a dialysatereservoir and not from a separate source of priming fluid.
 17. Thepriming process of claim 12 wherein said valve is placed in said firststate or second state by actuating a valve interface within saiddialysis machine.
 18. The priming process of claim 17 wherein said valveinterface is configured to apply pressure to, or remove pressure from,said compressible valve structure upon actuation by said controller. 19.The priming process of claim 18 wherein said compressible valvestructure is a diaphragm.
 20. The priming process of claim 1 whereinsaid compressible valve structure is a diaphragm.